Cross-species Analyses of Intra-species Behavioral Differences in Mammals and Fish

Multiple species display robust behavioral variance among individuals due to different genetic, genomic, epigenetic, neuroplasticity and environmental factors. Behavioral individuality has been extensively studied in various animal models, including rodents and other mammals. Fish, such as zebrafish (Danio rerio), have recently emerged as powerful aquatic model organisms with overt individual differences in behavioral, nociceptive and other CNS traits. Here, we evaluate individual behavioral differences in mammals and fish, emphasizing the importance of cross-species analyses of intraspecies variance in experimental models of normal and pathological CNS functions. © 2019 IBROAVK laboratory is supported by the Southwest University (Chongqing, China) Zebrafish Platform construction funds. This research is supported by the Russian Science Foundation grant 19-15-00053 . KAD is supported by the Russian Foundation for Basic Research ( RFBR) grant 18-34-00996 , Fellowship of the President of Russia and Special Rector’s Fellowship for SPSU PhD Students. DBR receives the CNPq research productivity grant (305051/2018-0), and his work is also supported by the PROEX/CAPES fellowhip grant 23038.004173/2019-93 (Brazil). MP receives funding from the British Academy (UK) . BDF is supported by a CAPES Foundation studentship (Brazil). FC is supported by the Father’s Foundation and the Fast Data Sharing-2036 programs. AVK is the Chair of the International Zebrafish Neuroscience Research Consortium (ZNRC) Special 2018-2019 Task Force that coordinated this multi-laboratory collaborative project

Delayed behavioral and genomic responses to acute combined stress in zebrafish, potentially relevant to PTSD and other stress-related disorders: Focus on neuroglia, neuroinflammation, apoptosis and epigenetic modulation

Stress is a common trigger of stress-related illnesses, such as anxiety, phobias, depression and post-traumatic stress disorder (PTSD). Various animal models successfully reproduce core behaviors of these clinical conditions. Here, we develop a novel zebrafish model of stress (potentially relevant to human stress-related disorders), based on delayed persistent behavioral, endocrine and genomic responses to an acute severe 'combined' stressor. Specifically, one week after adult zebrafish were exposed to a complex combined 90-min stress, we assessed their behaviors in the novel tank and the light-dark box tests, as well as whole-body cortisol and brain gene expression, focusing on genomic biomarkers of microglia, astrocytes, neuroinflammation, apoptosis and epigenetic modulation. Overall, stressed fish displayed persistent anxiety-like behavior, elevated whole-body cortisol, as well as upregulated brain mRNA expression of genes encoding the glucocorticoid receptor, neurotrophin BDNF and its receptors (TrkB and P75), CD11b (a general microglial biomarker), COX-2 (an M1-microglial biomarker), CD206 (an M2-microglial biomarker), GFAP (a general astrocytal biomarker), C3 (an A1-astrocytal biomarker), S100 alpha(10) (an A2-astrocytal biomarker), as well as pro-inflammatory cytokines IL-6, IL-1 beta, IFN-gamma and TNF-alpha. Stress exposure also persistently upregulated the brain expression of several key apoptotic (Bax, Caspase-3, Bcl-2) and epigenetic genes (DNMT3a, DNMT3b, HAT1, HDAC4) in these fish. Collectively, the present model not only successfully recapitulates lasting behavioral and endocrine symptoms of clinical stress-related disorders, but also implicates changes in neuroglia, neuroinflammation, apoptosis and epigenetic modulation in long-term effects of stress pathogenesis in vivo

The role of auditory and vibration stimuli in zebrafish neurobehavioral models

Strongly affecting human and animal physiology, sounds and vibration are critical environmental factors whose complex role in behavioral and brain functions necessitates further clinical and experimental studies. Zebrafish are a promising model organism for neuroscience research, including probing the contribution of auditory and vibration stimuli to neurobehavioral processes. Here, we summarize mounting evidence on the role of sound and vibration in zebrafish behavior and brain function, and outline future directions of translational research in this field. With the growing environmental exposure to noise and vibration, we call for more active use of zebrafish models for probing neurobehavioral and bioenvironmental consequences of acute and long-term exposure to sounds and vibration in complex biological systems

The role of auditory and vibration stimuli in zebrafish neurobehavioral models

Strongly affecting human and animal physiology, sounds and vibration are critical environmental factors whose complex role in behavioral and brain functions necessitates further clinical and experimental studies. Zebrafish are a promising model organism for neuroscience research, including probing the contribution of auditory and vibration stimuli to neurobehavioral processes. Here, we summarize mounting evidence on the role of sound and vibration in zebrafish behavior and brain function, and outline future directions of translational research in this field. With the growing environmental exposure to noise and vibration, we call for more active use of zebrafish models for probing neurobehavioral and bioenvironmental consequences of acute and long-term exposure to sounds and vibration in complex biological systems

Decoding the role of zebrafish neuroglia in CNS disease modeling

Neuroglia, including microglia and astrocytes, is a critical component of the central nervous system (CNS) that interacts with neurons to modulate brain activity, development, metabolism and signaling pathways. Thus, a better understanding of the role of neuroglia in the brain is critical. Complementing clinical and rodent data, the zebrafish (Danio rerio) is rapidly becoming an important model organism to probe the role of neuroglia in brain disorders. With high genetic and physiological similarity to humans and rodents, zebrafish possess some common (shared), as well as some specific molecular biomarkers and features of neuroglia development and functioning. Studying these common and zebrafish-specific aspects of neuroglia may generate important insights into key brain mechanisms, including neurodevelopmental, neurodegenerative, neuroregenerative and neurological processes. Here, we discuss the biology of neuroglia in humans, rodents and fish, its role in various CNS functions, and further directions of translational research into the role of neuroglia in CNS disorders using zebrafish models

Effects of acute and chronic arecoline in adult zebrafish: Anxiolytic-like activity, elevated brain monoamines and the potential role of microglia

Arecoline is a naturally occurring psychoactive alkaloid with partial agonism at nicotinic and muscarinic acetylcholine receptors. Arecoline consumption is widespread, making it the fourth (after alcohol, nicotine and caffeine) most used substance by humans. However, the mechanisms of acute and chronic action of arecoline in-vivo remain poorly understood. Animal models are a valuable tool for CNS disease modeling and drug screening. Complementing rodent studies, the zebrafish (Danio rerio) emerges as a promising novel model organism for neuroscience research. Here, we assessed the effects of acute and chronic arecoline on adult zebrafish behavior and physiology. Overall, acute and chronic arecoline treatments produced overt anxiolytic-like behavior (without affecting general locomotor activity and whole-body cortisol levels), with similar effects also caused by areca nut water extracts. Acute arecoline at 10 mg/L disrupted shoaling, increased social preference, elevated brain norepinephrine and serotonin levels and reduced serotonin turnover. Acute arecoline also upregulated early protooncogenes c-fos and c-jun in the brain, whereas chronic treatment with 1 mg/L elevated brain expression of microglia-specific biomarker genes egr2 and ym1 (thus, implicating microglial mechanisms in potential effects of long-term arecoline use). Finally, acute 2-h discontinuation of chronic arecoline treatment evoked withdrawal-like anxiogenic behavior in zebrafish. In general, these findings support high sensitivity of zebrafish screens to arecoline and related compounds, and reinforce the growing utility of zebrafish for probing molecular mechanisms of CNS drugs. Our study also suggests that novel anxiolytic drugs can eventually be developed based on arecoline-like molecules, whose integrative mechanisms of CNS action may involve monoaminergic and neuro-immune modulation